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MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms

Pierre-Yves Dumas1,2, Olivier Mansier3,4, Valerie Prouzet-Mauleon3

  • 1CHU de Bordeaux, Hématologie Clinique et Thérapie Cellulaire, F-33000, Bordeaux, France.

BMC Cancer
|November 14, 2018
PubMed
Abstract

Insights

MicroRNA-10a (miR-10a) is upregulated in atypical myeloproliferative neoplasms (aMPN) due to epigenetic dysregulation. This miR-10a overexpression, linked to HOXB4, may serve as a marker in aMPN pathogenesis.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Atypical myeloproliferative neoplasms (aMPN) share traits with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes.
  • The pathophysiology of aMPN remains unclear, despite known cytokine signaling abnormalities in MPN.
  • MicroRNA deregulation is implicated in various cancers, prompting investigation into the aMPN miRNome.

Purpose of the Study:

  • To investigate the miRNome of atypical myeloproliferative neoplasms (aMPN).
  • To explore the role of microRNAs, specifically miR-10a, and epigenetic regulators in aMPN.
  • To understand the functional impact of miR-10a and HOXB4 in hematopoietic cells.

Main Methods:

  • Analyzed miRNome and mutations in epigenetic genes (ASXL1, TET2, DNMT3A, EZH2, IDH1/2) in aMPN patients.
  • Investigated epigenetic regulation of miR-10a and HOXB4 using hematopoietic cell lines treated with epigenetic modifiers.
  • Assessed functional effects of miR-10a overexpression in normal hematopoietic stem cells.

Main Results:

  • MiR-10a was the most significantly upregulated microRNA in aMPN.
  • MiR-10a expression correlated with HOXB4, with co-transcription influenced by DNA demethylation and histone acetylation.
  • Overexpression of miR-10a and HOXB4 was associated with DNMT3A mutations but did not affect normal hematopoietic progenitor function.

Conclusions:

  • MiR-10a and HOXB4 are overexpressed in aMPN, likely due to epigenetic dysregulation.
  • The findings suggest miR-10a may be a marker for transcription at the HOXB4 locus in aMPN.
  • HOXB4 is recognized for its role in stem cell expansion, relevant to aMPN pathophysiology.
Keywords:
Atypical myeloproliferative neoplasmsDNMT3AEpigeneticHOXB4miR-10a

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